The Polymorphisms in <i>GSTO</i> Genes (<i>GSTO1</i> rs4925, <i>GSTO2</i> rs156697, and <i>GSTO2</i> rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study
Milos Petrovic,
Tatjana Simic,
Tatjana Djukic,
Tanja Radic,
Ana Savic-Radojevic,
Milica Zekovic,
Otas Durutovic,
Aleksandar Janicic,
Bogomir Milojevic,
Boris Kajmakovic,
Marko Zivkovic,
Nebojsa Bojanic,
Uros Bumbasirevic,
Vesna Coric
Affiliations
Milos Petrovic
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Tatjana Simic
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Tatjana Djukic
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Tanja Radic
Institute of Mental Health, 11000 Belgrade, Serbia
Ana Savic-Radojevic
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Milica Zekovic
Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia
Otas Durutovic
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Aleksandar Janicic
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Bogomir Milojevic
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Boris Kajmakovic
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Marko Zivkovic
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Nebojsa Bojanic
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Uros Bumbasirevic
Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Vesna Coric
Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Members of the omega class of glutathione transferases (GSTs), GSTO1, and GSTO2, catalyze a range of reduction reactions as a part of the antioxidant defense system. Polymorphisms of genes encoding antioxidant proteins and the resultant altered redox profile have already been associated with the increased risk for testicular germ cell cancer (GCT) development. The aim of this pilot study was to assess the individual, combined, haplotype, and cumulative effect of GSTO1rs4925, GSTO2rs156697, and GSTO2rs2297235 polymorphisms with the risk for testicular GCT development, in 88 patients and 96 matched controls, through logistic regression models. We found that carriers of the GSTO1*C/A*C/C genotype exhibited an increased risk for testicular GCT development. Significant association with increased risk of testicular GCT was observed in carriers of GSTO2rs2297235*A/G*G/G genotype, and in carriers of combined GSTO2rs156697*A/G*G/G and GSTO2rs2297235*A/G*G/G genotypes. Haplotype H7 (GSTO1rs4925*C/GSTO2rs2297235*G/GSTO2rs156697*G) exhibited higher risk of testicular GCT, however, without significant association (p > 0.05). Finally, 51% of testicular GCT patients were the carriers of all three risk-associated genotypes, with 2.5-fold increased cumulative risk. In conclusion, the results of this pilot study suggest that GSTO polymorphisms might affect the protective antioxidant activity of GSTO isoenzymes, therefore predisposing susceptible individuals toward higher risk for testicular GCT development.
